Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer.

The development of precision cancer medicine relies on novel formulation strategies for targeted drug delivery to increase the therapeutic outcome. Biocompatible polymer nanoparticles, namely dextran- graft -polyacrylamide (D- g -PAA) copolymers, represent one of the innovative non-invasive approaches for drug delivery applications in cancer therapy. In this study, the star-like D- g -PAA copolymer in anionic form (D- g -PAAan) was developed for pH-triggered targeted drug delivery of the common chemotherapeutic drugs - doxorubicin (Dox) and cisplatin (Cis). The initial D- g -PAA copolymer was synthesized by the radical graft polymerization method, and then alkaline-hydrolyzed to get this polymer in anionic form for further use for drug encapsulation. The acidification of the buffer promoted the release of loaded drugs. D- g -PAAan nanoparticles increased the toxic potential of the drugs against human and mouse lung carcinoma cells (A549 and LLC), but not against normal human lung cells (HEL299). The drug-loaded D- g -PAAan-nanoparticles promoted further oxidative stress and apoptosis induction in LLC cells. D- g -PAAan-nanoparticles improved Dox accumulation and drugs' toxicity in a 3D LLC multi-cellular spheroid model. The data obtained indicate that the strategy of chemotherapeutic drug encapsulation within the branched D- g -PAAan nanoparticle allows not only to realize pH-triggered drug release but also to potentiate its cytotoxic, prooxidant and proapoptotic effects against lung carcinoma cells.